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MiRNA-101在结直肠腺瘤及结直肠癌中表达差异的分析

发布时间:2018-12-24 08:10
【摘要】:结直肠癌是人类最常见的恶性肿瘤之一。其发病率在恶性肿瘤中分别占第三位,死亡率占恶性肿瘤的第四位,已经严重威胁着人们的健康,并对患者家庭造成了很大的疾病负担。部分患者在就诊时已发生远处转移,失去了手术机会。由于目前结直肠癌的发病率高,治疗效果不佳,特别是晚期癌症患者。因此,进一步探讨结直肠癌的发病机制,将为结直肠癌提供新的治疗方向。与其他恶性肿瘤一样,结直肠癌的发生一般是由癌基因的激活及抑癌基因的失活引起。但调节这些基因的生物学机制却仍处于研究阶段。自Lee等首次发现miRNA后,miRNA在生命活动中的作用机制不断被发掘,尤其是在肿瘤发生、发展中的作用。miRNA是一类高度保守的非编码小RNA,控制着约三分之一的人类基因的表达。miRNA一般通过调控癌基因或抑癌基因的信号通路来促进或抑制肿瘤的发生、发展,并在肿瘤的诊断、治疗及预后方面也起着重要的作用。miRNA-101作为miRNA家族中的一类,在人类多种肿瘤中呈表达下调,抑制肿瘤细胞的增殖,在肿瘤的发生、发展过程中扮演着抑癌基因的角色。既往有研究发现miRNA-101在结直肠癌中呈低表达,并通过不同靶基因抑制结直肠癌细胞的增殖、转移。但这些研究大部分是体外研究,且临床样本量较少。因此,本研究在这些研究的基础上扩大临床样本量,分析miRNA-101在结直肠腺瘤、结直肠癌组织中的表达情况,揭示其如何介导结直肠癌的发生,有助于为结直肠癌以后的诊断和治疗提供新的途径。目的:本研究将检测miRNA-101在结直肠腺瘤及结直肠癌组织中的表达是否有差异,并探讨其在结直肠癌发生过程中的作用。方法:本研究采用荧光定量PCR技术测定33例结直肠腺瘤患者(管状绒毛腺瘤8例,管状腺瘤25例)腺瘤组织及腺瘤旁正常组织,以及31例结直肠癌癌组织及癌旁正常组织中miRNA-101的相对表达量。本研究使用SPSS22.0统计学软件分析数据,因数据呈偏态分布,故采用配对设计符号秩和检验和两独立样本的秩和检验,P0.05认为差异有统计学意义。比较miRNA-101在腺瘤及癌中的表达是否有差异,分析其表达量与年龄、性别、病理类型等各临床病理资料之间的关系,并分析miRNA-101在结直肠癌的发生、发展中的作用。结果:(1)在结直肠腺瘤患者中,miRNA-101在腺瘤中的表达高于腺瘤旁组织(P0.05);(2)在腺瘤患者中,miRNA-101在不同性别,年龄及病理类型(即管状绒毛状腺瘤与管状腺瘤相比)中的相对表达量无差异,无统计学意义;(3)在结直肠癌患者中,miRNA-101癌组织中的表达低于癌旁组织(P0.05);(4)miRNA-101在结直肠癌患者在患者的各临床特征间(即性别、年龄、肿瘤部位)的相对表达量无差异,无统计学意义。结论:miRNA-101在腺瘤组织中表达升高,在结直肠癌组织中表达降低,提示其从正常结直肠组织到结直肠腺瘤,结直肠腺瘤到结直肠癌的发生发展过程中发挥了调控作用。本研究为miRNA-101作为结直肠癌预测、预后指标提供了实验基础。
[Abstract]:Colorectal cancer is one of the most common malignant tumors in humans. The incidence of the cancer is the third in the malignant tumor, and the death rate is the fourth of the malignant tumor, which has seriously threatened the health of the people, and has caused a great burden on the patient's family. Some of the patients had a distant metastasis at the time of the visit and the opportunity was lost. Because of the high incidence of colorectal cancer, the treatment effect is not good, especially in the patients with advanced cancer. Therefore, a further study of the pathogenesis of colorectal cancer will provide a new direction for the treatment of colorectal cancer. As with other malignant tumors, the occurrence of colorectal cancer is generally caused by the activation of the oncogene and the inactivation of the tumor suppressor gene. But the biological mechanism of regulating these genes is still in the research stage. After the first discovery of miRNAs, such as Lee, the role of miRNAs in life activities has been discovered, especially in the development of tumorigenesis and development. miRNA is a highly conserved non-coding small RNA that controls about one-third of the human gene expression. The miRNA is generally used to promote or inhibit the occurrence and development of the tumor by regulating the signal path of the oncogene or the tumor suppressor gene, and also plays an important role in the diagnosis, treatment and prognosis of the tumor. The miRNA-101 is used as a class in the miRNA family, the expression of the miRNA-101 is down-regulated in a plurality of tumors of the human, the proliferation of the tumor cells is inhibited, and the role of the tumor suppressor gene is played in the development and the development process of the tumor. Previous studies have found that miRNA-101 has a low expression in colorectal cancer and inhibits the proliferation and metastasis of colorectal cancer cells by different target genes. However, the majority of these studies were in vitro and the clinical sample size was small. Therefore, this study expanded the clinical sample size on the basis of these studies, and analyzed the expression of miRNA-101 in colorectal adenoma and colorectal cancer, and revealed how to mediate the occurrence of colorectal cancer and to provide a new way for the diagnosis and treatment of colorectal cancer. Objective: To study the expression of miRNA-101 in colorectal adenoma and colorectal cancer, and to explore the role of miRNA-101 in colorectal cancer. Methods: The relative expression of miRNA-101 in 33 patients with colorectal adenoma (8 cases of tubular villus adenoma, 25 cases of tubular adenoma), normal tissue of the adenoma, and 31 cases of colorectal cancer and the normal tissues of the adjacent normal tissues were determined by fluorescence quantitative PCR. In this study, the data was analyzed using the SPSS22. 0 statistical software, and the rank sum test of the paired design symbol and the rank and test of the two independent samples were used because of the bias distribution of the data, and the difference was considered to be of statistical significance. To compare the expression of miRNA-101 in adenoma and carcinoma, and to analyze the relationship between the expression of miRNA-101 and the clinical and pathological data of age, sex and pathological type, and to analyze the role of miRNA-101 in the development and development of colorectal cancer. Results: (1) In the patients with colorectal adenoma, the expression of miRNA-101 in the adenoma was higher than that of the adjacent adenoma (P0.05). (2) In the patients with adenoma, the relative expression of miRNA-101 in the different sex, age and pathological type (i.e., the tubular villous adenoma and the tubular adenoma) was not different. (3) The expression of miRNA-101 in the patients with colorectal cancer is lower than that of the adjacent tissues (P0.05). (4) The relative expression of miRNA-101 in the patients with colorectal cancer (i.e., sex, age, tumor site) has no difference and no statistical significance. Conclusion: The expression of miRNA-101 in the tissue of colorectal cancer is increased, and the expression of miRNA-101 in colorectal cancer is reduced, suggesting that it plays an important role in the development of colorectal adenoma, colorectal adenoma and colorectal cancer. The present study provided an experimental basis for miRNA-101 as a prognostic indicator for colorectal cancer.
【学位授予单位】:西南医科大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R735.34

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